Kimura's disease of the parapharyngeal space.

Abstract

Kimura's disease is a fairly uncommon inflammatory condition of unknown etiology. It classically presents in young Asian males as tumorlike subcutaneous nodules in the head and neck with associated lymphadenopathy, peripheral eosinophilia, and an elevated serum IgE level. Kimura's disease affects the subcutaneous tissues, salivary glands, and lymph nodes; less common sites in the head and neck include the eyelid and tympanic membrane. We report a case of Kimura's disease of the parapharyngeal space in a 42-year-old Chinese woman. To the best of our knowledge, this is the first report of Kimura's disease at this site.

Introduction

Kimura's disease is an uncommon condition of unknown etiology that classically presents as tumorlike subcutaneous nodules in the head and neck with associated lymphadenopathy, peripheraleosinophilia, and an elevated serum IgE level. It typically occurs in young Asian males; its incidence peaks in the second and third decades of life, and the male-to-female ratio is 3.5:1. (1) In this article, we describe a case of Kimura's disease that was unusual in two respects: it occurred in an middle-aged woman and, more notably, it occurred in the parapharyngeal space. To the best of our knowledge, this is the first reported case of Kimura's disease at this site.

Case report

A 42-year-old Chinese woman presented with a 2-month history of throat pain. She reported no epistaxis, nasal obstruction, dysphagia, hemoptysis, or other symptoms. She was a nonsmoker, and the rest of her medical history was unremarkable.

Examination revealed that a large (8 x 5 cm), nontender, longitudinally fusiform mass extended from the level of the right eustachian tube to the aryepiglottic told inferiorly. Nasal endoscopy showed that the mass protruded into the right nasopharynx and oropharynx. The overlying mucosa was intact and appeared to be normal. No lymphadenopathy or other abnormalities were found.

Computed tomography (CT) detected a mass in the parapharyngeal space with increased contrast uptake. Blood investigations revealed that the total leukocyte count was 8.4 x [10.sup.9]/L (normal: 4.0 to 10.0) and the eosinophil count was 13% (normal: 0 to 6%). Findings on all other investigations--namely, urea and electrolyte measurements, liver function tests, Epstein-Barr virus serology, and chest radiographs--were normal.

Histology of a transoral punch biopsy specimen revealed a reactive vascular proliferation with eosinophilic infiltration. This finding suggested either Kimura's disease or angiolymphoid hyperplasia with eosinophilia (ALHE). In order to make a definitive histologic diagnosis, we performed a wedge excision of the parapharyngeal space mass. The final histology identified a dense infiltrate of eosinophils in the submucosa and a few eosinophilic abscesses. Proliferation of small vessels lined with prominent enlarged vacuolated endothelial cells was seen. No germinal centers were noted, although interspersed plasma cells and lymphocytes were seen between the eosinophils. Residual normal-looking, mucus-secreting glands and ducts were present. In all, these findings were consistent with Kimura's disease.

The patient was given high-dose (40 mg/day) oral prednisolone for 6 months, hydroxyurea at 500 mg/day for 2 months, and 1 month of radiotherapy (34.2 Gy in fractions) to the head and neck. The tumor began to gradually shrink, and by 6 months it had disappeared. At that point, the patient was prescribed long-term prednisolone at 10 mg/day. At follow-up 4 years later, she was well and exhibited no evidence of recurrence.

Discussion

Kimura's disease was first described by Kimura et al in 1948. (2) The disease is believed to be a chronic allergic inflammatory condition of unknown origin. Disputes between investigators who believe it is immune-mediated and those who believe it is of infectious origin remain unresolved. The presence of immune complexes noted on immunofluorescence supports the possibility that Kimura's disease occurs secondary to au immunologic injury, (3) perhaps caused by an environmental or exogenous agent. (4)

Slowly growing subcutaneous masses of the head and neck are typical. Regional enlargement of lymph nodes (5) and parotid and submandibular salivary glands (6) can occur. Less common sites of involvement are the paranasal sinuses, kidneys, orbits, eyelids, (7) conjunctiva, (8) lacrimal glands, (9) epiglottis, (10) tympanic membrane, (11) and even the median nerve. (12) Renal involvement can lead to proteinuria and nephrotic syndrome. (13) Bronchial asthma in association with Kimura's disease has also been described. (14)

At one time, Kimura's disease and ALHE were believed to be one and the same. These terms were used interchangeably until the mid-1980s, when Kung et al (15) and Urabe et al (16) drew the distinction between the two entities:

* ALHE is believed to be neoplastic in origin and to represent a benign form of a spectrum of vascular proliferations, including epithelioid hemangioendothelioma and epithelioid angiosarcoma. ALHE usually occurs in Caucasians during the third to fifth decades of life. Patients typically present with small superficial subcutaneous lumps, no eosinophilia, and a normal IgE level.

* In contrast, Kimura's disease generally occurs in young Asian males who typically present with larger deep subcutaneous head and neck nodules. They also have peripheral eosinophilia (commonly >10%) and an elevated serum IgE level.

With regard to the histologic differences, ALHE is characterized by thick-walled vessels secondary to proliferation of "histiocytoid" endothelial cells, which are plump cells with large nuclei and abundant eosinophilic cytoplasm. (17) The key histologic features of Kimura's disease are eosinophilic abscesses in a background of an inflammatory infiltrate and proliferation of high endothelial venules (figure). IgE deposits in the germinal centers of Kimura's lesions may be an important differentiating factor. (18) Cellular atypia is never seen in Kimura's disease. (15)

In the case reported herein, our first clinical impression was that our patient had an 8 x 5-cm parapharyngeal space tumor that had probably arisen from the deep lobe of the parotid gland. The transoral punch biopsy revealed vascular proliferation with eosinophilia, which was suggestive of both Kimura's disease and ALHE. Considering our patient's race, the large and deep nature of the tumor, and the final histology obtained from the excision biopsy, the diagnosis of Kimura's disease was more likely--despite her age and sex.

The treatment of Kimura's disease is not well established. Surgery, corticosteroid therapy, and radiotherapy have all been used. Surgery has a crucial role in that it can establish the diagnosis while removing large compressive or cosmetically unacceptable lesions. Most authors believe that the recurrence rate is fairly high with surgical excision alone. (19) Corticosteroid therapy usually produces good results initially, but recurrence is common after discontinuation of therapy. Radiation has been used mainly to treat recalcitrant or large lesions. (20) Two other unestablished treatment modalities are cryotherapy and laser fulguration; the results of both are variable and very unpredictable. While recurrences are common, no case of metastasis or malignant degeneration has ever been reported. (6)

References

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(13.) Yamada A, Mitsuhashi K, Miyakawa Y, et al. Membranous glomerulonephritis associated with eosinophilic lymphofulliculosis of the skin (Kimura's disease): A report of a case and review of the literature. Clin Nephrol 1982:18:211-15.

(14.) Tsukagoshi H, Nagashima M. Horie T, et al. Kimura's disease associated with bronchial asthma presenting eosinophilia and hyperimmunnglobulinemia E which were attenuated by suplatast tosilate (IPD-115lT). Intern Med 1998:37:1064-7.

(15.) Kung IT. Gibson JB, Bannatyne PM. Kimura's disease: A clinicopathological study of 21 cases and its distinction from angiolymphoid hyperplasia with eosinophilia. Pathology 1984:16:39-44.

(16.) Urabe A, Tsuneyoshi M, Enjuji M. Epithelioid hemangioma versus Kimura's disease. A comparative clinicopathologic study. Am J Surg Pathol 1987;11:758-66.

(17.) Rosai J. Gold J. Landy R. The histiocytoid hemangiomas. A unifying concept embracing several previously described entities of skin. soft tissue, large vessels, bone, and heart. Hum Pathol 1979;10: 707-30.

(18.) Ishikawa E, Tanaka H, Kakimoto S, et al. A pathological study on eosinophilic lymphofolliculoid granuloma (Kimura's disease). Acta Pathol Jpn 1981:31:767-81.

(19.) Olsen TG, Helwig EB. Angiolymphoid hyperplasia with eosinophilia. A clinicopathologic study of 116 patients. J Am Acad Dermatol 1985:12:781-96.

(20.) Kina GE, Kim WC. Yang WI, et al. Radiation treatment in patients with recurrent Kimura's disease. Int J Radiat Oncol Biol Phys 1997:38:607-12.

Christopher Goh Hood Keng, FRCS, FAMS; Kenny Peter Pang, FRCS, MMed, FAMS; Poh Wee Teng, FRCPA, FAMS

From the Department of Otorhinolaryngology (Dr. Goh and Dr. Pang) and the Department of Pathology (Dr. Poh), Singapore General Hospital.

Reprint requests: Dr. Christopher Goh, Department of Otorhinolaryngology, Singapore General Hospital, Outram Rd., Singapore. Phone: [phone]: fax: [phone]: e-mail: [e-mail]